This Center grant was the first Specialized Research Center on brain tumors funded by the National Institute of Neurological Diseases and Stroke. It has focused on primary and metastatic tumors of the CNS of adults and children over its 25 year history. This application represents its sixth submission for competitive review and renewal. Primary and metastatic tumors of the CNS remain significant health problems in both adults and children, and this has been the research focus of this grant in the past. However, the focus of this new competitive renewal has turned to primary CNS tumors in adults only. Research on metastatic tumors and tumors of the CNS in children will continue at the Preston Robert Tisch Brain Tumor Center at Duke, but under separate funding mechanisms. Despite intensive research efforts by many investigators, there has been little progress in uncovering etiology or improving treatment of primary brain tumors during the last 30 years. This Specialized Research Center will continue brain tumor research efforts by including an outstanding group of internationally recognized investigators with a long history of effective collaboration. In this application, primary tumors in adults, both solid intracranial tumors and neoplastic meningitis, will be approached with novel therapeutic modalities. The three research projects include Project 1, a targeted radiotherapeutic approach utilizing modular recombinant transporters (MRT) labeled with Auger electron-emitting radionuclides;Project 2 utilizes an immunological approach with temozolomide-induced lymphopenia and a multivalent vaccine;and Project 3 includes multiple translational clinical trials for primary CNS tumors. Projects 1 and 3 are continuations of projects in the current grant. Project 2 is new to this SRC. Three Cores will support these research projects. They include an IND, Regulatory, and Bioinformatics Core (Core A);a Brain Tumor Biorepository, Histopathology, and Immunologic Monitoring Core (Core B), and an Administrative Core (Core C). Cores A and C are currently funded;Core B is a continuation from earlier grant periods. PUBLIC HEALTH RELEVANCE: This grant will support new and innovative approaches for the treatment of primary brain tumors in adults. Primary brain tumors remain an unmet medical need, and the likelihood of new effective treatments with acceptable toxicity should result from these efforts.